Pancreatic cancer (PCa) is one of the most devastating cancers with few clinical signs and no truly effective therapy. In recent years, our team has demonstrated that nucleolin antagonists such as N6L could be a therapeutic alternative for this disease. In order to study a possible clinic development of N6L (multivalent pseudopeptide), we undertook to study the effect of combination of N6L with chemotherapies classically used for PCa on the survival of pancreatic cancer cells. Thus, the combined effect of N6L with either gemcitabine, FOLFOX and paclitaxel (PTX) on the survival of PANC-1, Mia-PaCa-2 and BxPC3 was studied and shown additive effect. In addition, analysis of the data by Combenefit software indicates that there are synergistic effects between N6L and the 3 chemotherapy molecules tested with more sensitive effects with the N6L-PTX combination. This result was confirmed by associating N6L and paclitaxel on porous calcium carbonate particles loaded with cyclodextrin (CD) encapsulating PTX and carrying N6L at their surface. Porous calcium carbonate particles present highly benefits for biological purposes because of their large surface area and their high stability in neutral media. As for CD, it presents the advantage of owing hydrophilic exterior and a less polar cavity in the center. We have then combined the advantageous features of both porous and negatively charged surfaces of calcium carbonate (CaCO3) particles and host molecules CD for developing carrier enabling all at once the loading of PTX (hydrophobic drug) and N6L (cationic drug). This association generates water-soluble particles capable of targeting via N6L and delivering paclitaxel to tumor cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by poor prognosis, therapeutic resistance, and frequent recurrence. Current therapeutic options for PDAC include surgery, radiotherapy, immunological and targeted approaches. However, all these therapies provide only a slight improvement in patient survival. Consequently, the discovery of novel specific targets is becoming a priority to develop more effective treatments for PDAC. Mucin 1 (MUC1), a transmembrane glycoprotein, is aberrantly glycosylated and frequently overexpressed in pancreatic cancer. Recent studies highlighted the role of this oncoprotein in pancreatic carcinogenesis and its involvement in the acquisition of typical aggressive features of PDAC, like local invasion, metastases, and drug resistance. This review explores the mechanisms by which MUC1 contributes to cancer onset and progression, with a focus on its potential role as a biomarker and novel therapeutic target for pancreatic adenocarcinoma treatment.

To explore the value of laboratory serum markers and magnetic resonance imaging(MRI) features in the preoperative differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) in periampullary carcinoma (PAC).

A retrospective analysis of clinical data from 105 PAC patients who underwent pancreaticoduodenectomy was conducted, including 33 cases of PDAC (observation group) and 72 cases of non-PDAC (control group), with 25 cases of ampullary carcinoma, 38 cases of distal bile duct carcinoma, and 9 cases of periampullary duodenal carcinoma. Laboratory serum markers, MRI features, and pathological diagnosis data were compared between the two groups to analyze the value of laboratory serum markers and MRI features for differential diagnosis of PDAC within PAC.

Compared to the control group, the observation group had higher proportions in total bilirubin, direct bilirubin, carcinoembryonic antigen(CEA), carbohydrate antigen 19 - 9 (CA19-9), quadruple duct sign, pancreatobiliary junction angle, main pancreatic duct diameter, pancreatic head side branch duct dilation, and hypovascular mass in pancreatic head, consistency of imaging and pathology diagnosis, perineural invasion (p < 0.05).The common bile duct diameter was smaller in the observation group (p < 0.05). The sensitivities of CA19-9, main pancreatic duct diameter, pancreatic head side branch duct dilation, and hypovascular mass in pancreatic head in PDAC within PAC are 53.8%, 51%, 84.6%, and 81.1%, respectively; the specificities are 81.8%, 87%, 86.1%, and 95.6%, respectively; and the areas under the ROC curve are 0.74, 0.749, 0.806, and 0.906, respectively.

In the preoperative diagnosis of PAC, CA19-9, main pancreatic duct diameter, hypovascular mass in pancreatic head, and pancreatic head side branch duct dilation are effective indicators for distinguishing PDAC.

We present a case of pancreatic ductal adenocarcinoma showing increased 68 Ga-DOTATATE uptake mimicking neuroendocrine tumor on PET/CT. Immunohistochemical analyses of the resected tumor showed the tumor cells were negative for somatostatin receptor subtype 2. The nonneoplastic islets scattered throughout the tumor were positive for somatostatin receptor subtype 2, which may be responsible for the increased 68 Ga-DOTATATE uptake. This case indicates that pancreatic ductal adenocarcinoma should be included in the differential diagnosis of the pancreatic lesions showing increased 68 Ga-DOTATATE uptake.

Based on the Fukuoka and Kyoto international consensus guidelines, the current clinical management of intraductal papillary mucinous neoplasm (IPMN) largely depends on imaging features. While these criteria are highly sensitive in detecting high-risk IPMN, they lack specificity, resulting in surgical overtreatment. Artificial Intelligence (AI)-based medical image analysis has the potential to augment the clinical management of IPMNs by improving diagnostic accuracy.

Based on a systematic review of the academic literature on AI in IPMN imaging, 1041 publications were identified of which 25 published studies were included in the analysis. The studies were stratified based on prediction target, underlying data type and imaging modality, patient cohort size, and stage of clinical translation and were subsequently analyzed to identify trends and gaps in the field.

Research on AI in IPMN imaging has been increasing in recent years. The majority of studies utilized CT imaging to train computational models. Most studies presented computational models developed on single-center datasets (n=11,44%) and included less than 250 patients (n=18,72%). Methodologically, convolutional neural network (CNN)-based algorithms were most commonly used. Thematically, most studies reported models augmenting differential diagnosis (n=9,36%) or risk stratification (n=10,40%) rather than IPMN detection (n=5,20%) or IPMN segmentation (n=2,8%).

This systematic review provides a comprehensive overview of the research landscape of AI in IPMN imaging. Computational models have potential to enhance the accurate and precise stratification of patients with IPMN. Multicenter collaboration and datasets comprising various modalities are necessary to fully utilize this potential, alongside concerted efforts towards clinical translation.

Undifferentiated carcinoma (UC) is a rare subtype of pancreatic cancer distinguished from UC with osteoclast-like giant cells (UC-OGC) in 2019, affecting interpretation of literature that does not distinguish these subtypes. We sought to identify translationally relevant differences between these 2 variants and compared with pancreatic ductal adenocarcinoma.

We characterized clinical and multiomic differences between UC (n = 32) and UC-OGC (n = 15) using DNA sequencing, RNA sequencing, and multiplex immunofluorescence and compared these findings with pancreatic ductal adenocarcinoma.

Characteristics at diagnosis were similar between UC and UC-OGC, though the latter was more resectable (P = .009). Across all stages, median overall survival was shorter for UC than for UC-OGC (0.4 years vs 10.8 years, respectively; P = .003). This shorter survival was retained after stratification by resection, albeit without statistical significance (1.8 years vs 11.9 years, respectively; P = .08). In a subset of patients with available tissue, the genomic landscape was similar among UC (n = 9), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 159). Bulk RNA sequencing was deconvoluted and, along with multiplex immunofluorescence in UC (n = 13), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 16), demonstrated statistically significantly increased antigen-presenting cells, including M2 macrophages and natural killer cells, and decreased cytotoxic and regulatory T cells in UC and UC-OGC vs pancreatic ductal adenocarcinoma. Findings were similar between UC and UC-OGC , except for decreased regulatory T cells in UC-OGC (P = .04).

In this series, UC was more aggressive than UC-OGC, with these variants having more antigen-presenting cells and fewer regulatory T cells than pancreatic ductal adenocarcinoma, suggesting potential for immune-modulating therapies in the treatment of these pancreatic cancer subtypes.

Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer (PC), with no established consensus on the optimal treatment for postoperative liver metastasis recurrence. We report a case of a 48-year-old male patient who underwent radical surgery and was pathologically diagnosed with microsatellite instability-high (MSI-H) PASC. The patient experienced liver metastasis recurrence following single-agent gemcitabine adjuvant chemotherapy. After one session of transarterial chemoembolization (TACE) with oxaliplatin, fluorouracil, and epirubicin, followed by six cycles of adjuvant chemotherapy with gemcitabine and nab-paclitaxel combined with sintilimab immunotherapy and bevacizumab targeted therapy, complete pathological regression of the liver metastasis was achieved. The patient has now reached a 24-month survival period and continues to be monitored at our center. This case illustrates the promise of the proposed treatment regimen, highlighting the significant potential of multimodality strategies in managing metastatic recurrence of MSI-H PASC.

To explore the diagnostic efficacy of advanced intelligent clear-IQ engine (AiCE) and adaptive iterative dose reduction 3D (AIDR 3D), combination with and without the black blood CT technique (BBCT), for detecting vascular invasion in patients diagnosed with nonmetastatic pancreatic ductal adenocarcinoma (PDAC).

A total of 35 consecutive patients diagnosed with PDAC, proceeding with contrast-enhanced abdominal CT scans, were enrolled in this study. The arterial and portal venous phase images were reconstructed using AiCE and AIDR 3D. The corresponding BBCT images were established as AiCE-BBCT and AIDR 3D-BBCT, respectively. Two observers scored the image quality independently. Cohen's kappa (k) value or intraclass correlation coefficient (ICC) was used to analyze consistency. The diagnostic performance of four algorithms in detecting vascular invasion in PDAC patients was assessed using the area under the curve (AUC).

The AiCE and AiCE-BBCT groups demonstrated superior image noise and diagnostic acceptability compared with AIDR 3D and AIDR 3D-BBCT groups (all p < 0.001), and the k value was 0.861-0.967 for both reviewers. In terms of diagnostic capability for vascular invasion in PDAC, the AiCE-BBCT group exhibited higher specificity (95.0%) and sensitivity (93.3%) compared to the AIDR 3D and AIDR 3D-BBCT groups, with an AUC of 0.942 (95% CI: 0.849-1.000, p < 0.05). Furthermore, all vascular evaluations conducted using AiCE-BBCT demonstrated better consistency (ICC: 0.847-0.935).

The BBCT technique in conjunction with AiCE could lead to notable enhancements in both the image quality of PDAC images and the diagnostic performance for tumor vascular invasion.

Better diagnostic accuracy of vascular invasion of PDAC based on BBCT in combination with an AiCE is a critical factor in determining treatment strategies and patient outcomes.

Identifying vascular invasion of PDAC is important for prognostication. Combined images provide improved image quality and higher diagnostic accuracy. Combined images can excellently display the vascular wall and invasion.

Solitary pancreatic metastasis is a rare cause of pancreatic neoplasm. Pancreatic ductal adenocarcinoma is the primary differential consideration when a solitary pancreatic mass is diagnosed, as it is the most common solitary solid pancreatic neoplasm. A majority of pancreatic ductal adenocarcinomas arise in the region of the head of the pancreas; however, specific neoplastic and non-neoplastic lesions can occur at or adjacent to the pancreatic head, which can mimic a pancreatic ductal adenocarcinoma. Therefore, a histopathological diagnosis is essential for confirming pancreatic ductal adenocarcinoma. Isolated solitary metastasis from primary lung adenocarcinoma is a rare cause of a solitary pancreatic head mass. We report a case in which imaging and pathology were integral to the diagnosis of a solitary lung adenocarcinoma metastasis to the head of the pancreas, which ultimately guided appropriate patient management.

Hepatoid adenocarcinoma of the pancreas is a rare aggressive tumor with poor prognosis. We describe contrast-enhanced CT and FDG PET/CT findings in a case of pancreatic hepatoid adenocarcinoma with significantly elevated α-fetoprotein level presenting as acute pancreatitis. The primary pancreatic tumor diffusely involved the pancreas and showed heterogeneous enhancement mimicking acute necrotizing pancreatitis on contrast-enhanced CT. FDG PET/CT showed intense FDG uptake (SUV max , 24.5) of the left supraclavicular and retroperitoneal lymph node metastases, suggesting FDG PET/CT may be useful for staging of this aggressive tumor.

Groove pancreatitis (GP) is a rare and clinically distinct form of chronic pancreatitis affecting the pancreaticoduodenal groove comprising the head of the pancreas, duodenum, and the common bile duct. It is more prevalent in individuals in their 4-5th decade of life and disproportionately affects men compared with women. Excessive alcohol consumption, tobacco smoking, pancreatic ductal stones, pancreatic divisum, annular pancreas, ectopic pancreas, duodenal wall thickening, and peptic ulcers are significant risk factors implicated in the development of GP. The usual presenting symptoms include severe abdominal pain, nausea, vomiting, diarrhea, weight loss, and jaundice. Establishing a diagnosis of GP is often challenging due to significant clinical and radiological overlap with numerous benign and malignant conditions affecting the same anatomical location. This can lead to a delay in initiation of treatment leading to increasing morbidity, mortality, and complication rates. Promising research in artificial intelligence (AI) has garnered immense interest in recent years. Due to its widespread application in diagnostic imaging with a high degree of sensitivity and specificity, AI has the potential of becoming a vital tool in differentiating GP from pancreatic malignancies, thereby preventing a missed or delayed diagnosis. In this article, we provide a comprehensive review of GP, covering the etiology, pathogenesis, clinical presentation, radiological and endoscopic evaluation, management strategies, and future directions. This article also aims to increase awareness about this lesser known and often-misdiagnosed clinical entity amongst clinicians to ultimately improve patient outcomes.

Abnormal sphingolipid metabolism (SM) is closely linked to the incidence of cancers. However, the role of SM in pancreatic cancer (PC) remains unclear. This study aims to explore the significance of SM in the prognosis, immune microenvironment, and treatment of PC.

Single-cell and bulk transcriptome data of PC were acquired via TCGA and GEO databases. SM-related genes (SMRGs) were obtained via MSigDB database. Consensus clustering was utilized to construct SM-related molecular subtypes. LASSO and Cox regression were utilized to build SM-related prognostic signature. ESTIMATE and CIBERSORT algorithms were employed to assess the tumour immune microenvironment. OncoPredict package was used to predict drug sensitivity. CCK-8, scratch, and transwell experiments were performed to analyze the function of ANKRD22 in PC cell line PANC-1 and BxPC-3.

A total of 153 SMRGs were acquired, of which 48 were linked to PC patients' prognosis. Two SM-related subtypes (SMRGcluster A and B) were identified in PC. SMRGcluster A had a poorer outcome and more active SM process compared to SMRGcluster B. Immune analysis revealed that SMRGcluster B had higher immune and stromal scores and CD8 + T cell abundance, while SMRGcluster A had a higher tumour purity score and M0 macrophages and activated dendritic cell abundance. PC with SMRGcluster B was more susceptible to gemcitabine, paclitaxel, and oxaliplatin. Then SM-related prognostic model (including ANLN, ANKRD22, and DKK1) was built, which had a very good predictive performance. Single-cell analysis revealed that in PC microenvironment, macrophages, epithelial cells, and endothelial cells had relatively higher SM activity. ANKRD22, DKK1, and ANLN have relatively higher expression levels in epithelial cells. Cell subpopulations with high expression of ANKRD22, DKK1, and ANLN had more active SM activity. In vitro experiments showed that ANKRD22 knockdown can inhibit the proliferation, migration, and invasion of PC cells.

This study revealed the important significance of SM in PC and identified SM-associated molecular subtypes and prognostic model, which provided novel perspectives on the stratification, prognostic prediction, and precision treatment of PC patients.

Pancreatic ductal adenocarcinoma (PDAC) can be classified into distinct histological subtypes based on the WHO nomenclature. The aim of this study was to compare the prognosis of conventional PDAC (cPDAC) against the other histological variants at the population level.

The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients with microscopically confirmed PDAC. These patients were divided into 9 histological subgroups. Overall survival was assessed using the Kaplan-Meier method and Cox regression models stratified by tumor histology.

A total of 159,548 patients with PDAC were identified, of whom 95.9% had cPDAC, followed by colloid carcinoma (CC) (2.6%), adenosquamous carcinoma (ASqC) (0.8%), signet ring cell carcinoma (SRCC) (0.5%), undifferentiated carcinoma (UC) (0.1%), undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) (0.1%), hepatoid carcinoma (HC) (0.01%), medullary carcinoma of the pancreas (MCP) (0.006%) and pancreatic undifferentiated carcinoma with rhabdoid phenotype (PUCR) (0.003%). Kaplan-Meier curves showed that PUCR had the worst prognosis (median survival: 2 months; 5-year survival: 0%), while MCP had the best prognosis (median survival: 41 months; 5-year survival: 33.3%). In a multivariable Cox model, several histological subtypes (i.e. CC, ASqC, SRCC, UCOGC) were identified as independent predictors of overall survival when compared to cPDAC.

PDAC is a heterogenous disease and accurate identification of variant histology is important for risk stratification, as these variants may have different biological behavior.

The diagnostic approach to solid pancreatic masses has significantly evolved from the era when a focal pancreatic mass was almost synonymous to pancreatic ductal adenocarcinoma, to a wide spectrum of pancreatic lesions, some of which have good prognosis. With the advent of advanced diagnostic tools, particularly refined imaging and tissue acquisition techniques, a broader spectrum of differential diagnoses has been recognized, encompassing conditions ranging from neuroendocrine tumors or inflammatory masses, to rare entities like metastatic clear cell sarcoma or solitary fibrous tumors. We herein discuss case reports of some rare pancreatic lesions, which were diagnosed by combining clinical and imaging features and endoscopic ultrasound-guided tissue sampling and confirmed on surgical specimens. Further reports on these rare pancreatic tumors will contribute to a better understanding of their pathogenesis and effective management.

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort.

A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk.

Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68-0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84-1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42-0.85] P = 0.004) compared to non-use.

Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM.

Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis.

Pancreatic cancer is still a difficult disease to treat, despite recent advances in surgical techniques and chemotherapeutic drugs. Its incidence continues to rise, as does the number of older patients. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. Sarcopenia is present in approximately 40% in patients with pancreatic cancer. Sarcopenia is primarily diagnosed through imaging, and progress is being made in the development of automated methods and artificial intelligence, as well as biomarker research. Sarcopenia has been linked to a poor prognosis in pancreatic cancer patients. However, some studies suggest that sarcopenia is not always associated with a poor prognosis, depending on the resectability of pancreatic cancer and the nature of treatment, such as surgery or chemotherapy. Recent meta-analyses have found that sarcopenia is not linked to postoperative complications. It is still debated whether there is a link between sarcopenia and drug toxicity during chemotherapy. The relationship between sarcopenia and immunity has been investigated, but the mechanism is still unknown.

We report a case of a 44-year-old male patient, who presented to the University Hospital of Salzburg, Austria with abdominal pain, persistent jaundice, and lack of appetite. Radiological work-up (CT, MRI, PET/CT) indicated a suspicious mass of the uncinate process of the pancreatic head with adjacent infiltration and regional lymphadenopathy. The differential diagnosis was between primary pancreatic cancer and focal autoimmune pancreatitis. Further laparoscopic biopsies from multiple areas, showed only fibrous scarring processes, with no malignancy. Treatment with steroids didn't give any benefits. After multiple follow-up CTs and MRs within 6 months-additional biopsies were done, which eventually demonstrated adenocarcinoma. Evidently the cancer diagnosis was much delayed and the patient started receiving chemotherapy, but radical surgery was not possible. Multiple articles and case reports can be found in the literature, that are reviewing the fact that pancreatic inflammatory processes are mimicking pancreatic tumor, but not many articles or case reports are available in the literature, where neoplastic processes are misinterpreted as inflammatory and incorrectly proven with histological examination. One of the main reasons for improper diagnosis is the desmoplastic reaction around the pancreatic malignancy. Another important aspect is the acceptance of histological diagnosis as conclusive, where no opposing arguments are specified, based on radiological criteria.

Pancreatic cancer is one of the deadliest malignancies in humans and it is expected to play a bigger part in cancer burden in the years to come. Pancreatic ductal adenocarcinoma (PDAC) represents 85% of all primary pancreatic malignancies. Recently, much attention has been given to PDAC, with significant advances in the understanding of the mechanisms underpinning disease initiation and progression, along with noticeable improvements in overall survival in both localized and metastatic settings. However, given their rarity, rare histological subtypes of pancreatic cancer have been underappreciated and are frequently treated as PDAC, even though they might present non-overlapping molecular alterations and clinical behavior. While some of these rare histological subtypes are true variants of PDAC that should be treated likewise, others represent separate clinicopathological entities, warranting a different therapeutic approach. In this review, we highlight clinical, pathological, and molecular aspects of rare histological types of pancreatic cancer, along with the currently available data to guide treatment decisions.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is a rare pancreatic tumor that accounts for less than 1% of all pancreatic malignancies. The characteristic pathological manifestation of UCOGCP is the presence of osteoclast-like giant cells (OGCs) distributed among pleomorphic undifferentiated tumor cells. UCOGCP can occur either alone or in association with other types of pancreatic tumors. At present, there is no unified consensus or guideline for the diagnosis and treatment of UCOGCP, and most of the literature are individual case reports. With the accumulation in the number of clinical cases and the development of precision medicine technology, the understanding of UCOGCP is also deepening. Researchers have begun to recognize that UCOGCP is a pancreatic tumor with distinctive clinical and molecular characteristics. In this review, we focus on the latest research status and future exploration directions in the diagnosis, treatment, and prognosis of UCOGCP.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death by 2030. The diagnosis at a late stage is the underlying cause for higher mortality and poor prognosis after surgery. Treatment resistance to chemotherapy and immunotherapy results in recurrence after surgery and poor prognosis. Neoantigen burden and CD8+ T-cell infiltration are associated with clinical outcomes in PDAC and paucity of neoantigen-reactive tumor-infiltrating lymphocytes may be the underlying cause for treatment resistance for immunotherapy. This suggests a need to identify additional neoantigens and therapies targeting these neoantigens to improve clinical outcomes in PDAC. In this review, we focus on describing the pathophysiology, current treatment strategies, and treatment resistance in PDAC followed by the need to target neoantigens in PDAC.

Radiological studies play a crucial role in the evaluation of patients with biliary duct obstruction, allowing for the guidance of clinical diagnosis towards a malignant or stone-induced etiology through the recognition of relevant imaging features, which must be continuously revisited given their prognostic significance. This article aims to emphasize the importance of recognizing crucial imaging aspects of malignant and stone-induced biliary obstruction.

To compare the diagnostic performance of 40 keV and 70 keV virtual monoenergetic images (VMIs) generated from dual-energy CT in the detection of pancreatic cancer.

This retrospective study included patients who underwent pancreatic protocol dual-energy CT from January 2019 to August 2022. Four radiologists (1-11 years of experience), who were blinded to the final diagnosis, independently and randomly interpreted 40 keV and 70 keV VMIs and graded the presence or absence of pancreatic cancer. For each image set (40 keV and 70 keV VMIs), the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. The diagnostic performance of each image set was compared using generalized estimating equations.

Overall, 137 patients (median age, 71 years; interquartile range, 63-78 years; 77 men) were included. Among them, 62 patients (45%) had pathologically proven pancreatic cancer. The 40 keV VMIs had higher specificity (75% vs. 67%; P < .001), PPV (76% vs. 71%; P < .001), and accuracy (85% vs. 81%; P = .001) than the 70 keV VMIs. On the contrary, 40 keV VMIs had lower sensitivity (96% vs. 98%; P = .02) and NPV (96% vs. 98%; P = .004) than 70 keV VMIs. However, the diagnostic confidence in patients with (P < .001) and without (P = .001) pancreatic cancer was improved in 40 keV VMIs than in 70 keV VMIs.

The 40 keV VMIs showed better diagnostic performance in diagnosing pancreatic cancer than the 70 keV VMIs, along with higher reader confidence.

Pancreatic cancer is one of the most lethal malignancies. Even though many substantial improvements in the survival rates for other major cancer forms were made, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Even more, no standard classification system for pancreatic cancer is based on cellular biomarkers. This review will discuss and provide updates about the role of stem cells in the progression of PC, the genetic changes associated with it, and the promising biomarkers for diagnosis.

The search process used PubMed, Cochrane Library, and Scopus databases to identify the relevant and related articles. Articles had to be published in English to be considered.

The increasing number of studies in recent years has revealed that the diversity of cancer-associated fibroblasts is far greater than previously acknowledged, which highlights the need for further research to better understand the various cancer-associated fibroblast subpopulations. Despite the huge diversity in pancreatic cancer, some common features can be noted to be shared among patients. Mutations involving CDKN2, P53, and K-RAS can be seen in a big number of patients, for example. Similarly, some patterns of genes and biomarkers expression and the level of their expression can help in predicting cancer behavior such as metastasis and drug resistance. The current trend in cancer research, especially with the advancement in technology, is to sequence everything in hopes of finding disease-related mutations.

Optimizing pancreatic cancer treatment requires clear classification, understanding CAF roles, and exploring stroma reshaping approaches.

Nivolumab with modified FOLFIRINOX (mFOLFIRINOX) may have additive antitumour effects while minimising chemotherapy cytotoxicity. We assessed the efficacy and safety of nivolumab+mFOLFIRINOX in metastatic pancreatic cancer.

Thirty-one treatment-naïve patients aged ≥20 years with metastatic unresectable/recurrent pancreatic cancer (≥1 measurable lesion per Response Evaluation Criteria in Solid Tumours version 1.1) and Eastern Cooperative Oncology Group 0/1 score and life expectancy ≥90 days received nivolumab (480 mg, every 4 weeks) plus mFOLFIRINOX. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety.

At the median follow-up of 13.4 months, the ORR was 32.3% (complete response 0%; partial response 32.3%) and the median duration of response was 7.4 (range: 3.5-21.9) months; the primary endpoint was not met. Median OS and PFS were 13.4 (95% confidence interval [CI]: 10.6-16.6) months and 7.4 (95% CI: 3.9-9.2) months, respectively. The 1-year survival rate was 54.8% (95% CI: 36.0%-70.3%). Drug-related serious adverse events were reported in 29.0% of the patients; 3.2% drug-related adverse events led to discontinuation, and none led to death within 30-day safety window.

Nivolumab+mFOLFIRINOX was tolerable in patients with metastatic pancreatic cancer. ORR and survival were comparable to previously reported data. (JapicCTI-184230).

Pancreatic cancer (PC) remains a leading cause of mortality worldwide due to the absence of early detection methods and the low success rates of traditional therapeutic strategies. Drug resistance in PC is driven by its desmoplastic stroma, which creates a barrier that shields cancer niches and prevents the penetration of drugs. The PC stroma comprises heterogeneous cellular populations and non-cellular components involved in aberrant ECM deposition, immunosuppression, and drug resistance. These components can influence PC development through intricate and complex crosstalk with the PC cells. Understanding how stromal components and cells interact with and influence the invasiveness and refractoriness of PC cells is thus a prerequisite for developing successful stroma-modulating strategies capable of remodeling the PC stroma to alleviate drug resistance and enhance therapeutic outcomes. In this review, we explore how non-cellular and cellular stromal components, including cancer-associated fibroblasts and tumor-associated macrophages, contribute to the immunosuppressive and tumor-promoting effects of the stroma. We also examine the signaling pathways underlying their activation, tumorigenic effects, and interactions with PC cells. Finally, we discuss recent pre-clinical and clinical work aimed at developing and testing novel stroma-modulating agents to alleviate drug resistance and improve therapeutic outcomes in PC.

Pancreatic squamous cell carcinoma is a rare type of pancreatic cancer of ductal origin, composing an estimated 0.5 - 5% of pancreatic ductal malignancies. As a result, epidemiology, treatment options, and associated outcomes are poorly understood and understudied. Our aim was two-fold: to evaluate demographic trends and analyze overall survival (OS) associated with different treatment modalities for this rare malignancy.

Patients with pancreatic squamous cell carcinoma diagnosed between 1992 and 2019 were eligible and reviewed utilizing the Surveillance, Epidemiology, and End Results Registry (SEER) database. Data was analyzed using SPSS and python packages lifelines and pandas. Variables of interest included stage at diagnosis as well as the receipt of surgery, radiotherapy, and/or chemotherapy. Five-year OS curves were analyzed using Kaplan-Meier probability stratified by treatment modality.

Of 342 cases of pancreatic squamous cell carcinoma, 170 (49.7%) were females and 172 (50.3%) were males. 72 (21.1%) of patients received radiotherapy, 123 (35.9%) patients received chemotherapy, and 47 (13.7%) received surgery. Patients who were diagnosed under the age of 50 had prolonged survival time compared to those diagnosed over the age of 50 (12 vs 8 months, respectively, p < 0.001). This trend was evident despite the lack of a significant association between age at diagnosis and presence of metastases (p = 0.524). The median OS was 3 months for the entire cohort and there was a significant difference in median survival time noted across treatment modalities: OS was prolonged in those receiving surgery compared to those receiving chemotherapy or radiotherapy alone (30 vs 2 months, respectively, (p<0.001)). Receipt of radiotherapy was not associated with a significant difference in OS compared to those who did not receive radiotherapy.

Pancreatic squamous cell carcinoma is a rare subtype of pancreatic cancer and typically portends a poor prognosis. As demonstrated by our study, surgery offers prolonged overall survival compared to other treatment modalities. Age at diagnosis and presence of metastatic disease are also important prognostic factors likely related to patients' ability to tolerate surgery or physician willingness to offer surgery. Given the importance of surgery on outcomes, it may be reasonable to offer it in the oligometastatic setting in patients who are otherwise a good candidate. Future research on larger cohorts is warranted to investigate the role that modality selection plays in overall survival rates in this understudied malignancy.

To investigate the imaging characteristics of large duct pancreatic ductal adenocarcinoma (LD-PDAC) on computed tomography (CT) and magnetic resonance imaging (MRI).

Thirty-five patients with LD-PDAC (63.2 ± 9.7 years) were retrospectively evaluated. Tumor morphology on CT and MRI (predominantly solid mass vs. solid mass with prominent cysts vs. predominantly cystic mass) was evaluated. Additionally, the visibility, quantity, shape (oval vs. branching vs. irregular), and MRI signal intensity of neoplastic cysts within the LD-PDAC were investigated. The radiological diagnoses rendered for LD-PDAC in radiology reports were reviewed.

LD-PDAC was more commonly observed as a solid mass with prominent cysts (45.7% [16/35] on CT and 37.1% [13/35] on MRI) or a predominantly cystic mass (20.0% [7/35] on CT and 40.0% [14/35] on MRI) and less commonly as a predominantly solid mass on CT (34.3% [12/35]) and MRI (22.9% [8/35]). The tumor morphology on imaging was significantly associated with the size of the cancer gland on histopathological examination (P = 0.020 [CT] and 0.013 [MRI]). Neoplastic cysts were visible in 88.6% (31/35) and 91.4% (32/35) of the LD-PDAC cases on CT and MRI, respectively. The cysts appeared as branching (51.6% [16/35] on CT and 59.4% [19/35] on MRI) or oval shapes (45.2% [14/35] on CT and 31.2% [10/35] on MRI) with fluid-like MRI signal intensity. In the radiology reports, 10 LD-PDAC cases (28.6%) were misinterpreted as diseases other than typical PDAC, particularly intraductal papillary mucinous neoplasms.

LD-PDAC frequently appears as a solid mass with prominent cysts or as a predominantly cystic mass on CT and MRI. Radiologists should be familiar with the imaging features of LD-PDAC to avoid misdiagnosis.

In rare cases, metastatic adenocarcinomas of different origin may exhibit the features of hepatoid carcinoma (HC), a rare malignant epithelial tumor, most commonly occurring in the ovaries and stomach, as well as in the pancreas and biliary ducts. A case of a 72-year-old female patient who developed a highly aggressive, poorly differentiated pancreatic ductal adenocarcinoma with peritoneal carcinomatosis, demonstrating hepatoid differentiation upon conventional hematoxylin and eosin staining is reported in the present study. The patient presented with severe abdominal pain, and the radiological investigations performed revealed ovarian and hepatic tumor masses and peritoneal lesions, which were surgically removed. The gross examination of the peritoneum and omentum revealed multiple solid, firm, grey-white nodules, diffusely infiltrating the adipose tissue. The microscopic examination revealed a malignant epithelial proliferation, composed of polygonal cells with abundant eosinophilic cytoplasm and irregular, pleomorphic nuclei. Certain cells presented with intracytoplasmic mucus inclusions, raising suspicion of a HC with an uncertain histogenesis. Immunohistochemical staining was performed, and the tumor cells were found to be positive for cytokeratin (CK)7, CK18 and mucin 5AC, whereas negative staining for CK20, caudal-type homeobox transcription factor 2, α-fetoprotein, paired box gene 8, GATA-binding protein 3 and Wilms tumor 1 were documented. Thus, the diagnosis of metastatic pancreatic adenocarcinoma was established. The main aim of the present study was to provide further knowledge concerning poorly differentiated metastatic adenocarcinoma resembling HC, emphasizing the histopathological and immunohistochemical features of these malignant lesions and raising awareness of the diagnostic difficulties that may arise, as well as the importance of the use immunohistochemistry in differentiating carcinomas of uncertain histogenesis.

Signet-ring cell (SRC)/poorly cohesive cell carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its clinicopathologic and molecular profiles based on a multi-institutional cohort of 20 cases. The molecular profiles were investigated using DNA and RNA sequencing. The clinicopathologic parameters and molecular alterations were analyzed based on survival indices and using a validation/comparative cohort of 480 conventional PDAC patients. The primary findings were as follows: (1) clinicopathologic features: SRC carcinomas are highly aggressive neoplasms with poor prognosis, and the lungs are elective metastatic sites; (2) survival analysis: a higher SRC component was indicative of poorer prognosis. In particular, the most clinically significant threshold of SRC was 80%, showing statistically significant differences in both disease-specific and disease-free survival; (3) genomic profiles: SRC carcinomas are similar to conventional PDAC with the most common alterations affecting the classic PDAC drivers KRAS (70% of cases), TP53 (55%), SMAD4 (25%), and CDKN2A (20%). EGFR alterations, RET::CCDC6 fusion gene, and microsatellite instability (3 different cases, 1 alteration per case) represent novel targets for precision oncology. The occurrence of SMAD4 mutations was associated with poorer prognosis; (4) pancreatic SRC carcinomas are genetically different from gastric SRC carcinomas: CDH1, the classic driver gene of gastric SRC carcinoma, is not altered in pancreatic SRC carcinoma; (5) transcriptome analysis: the cases clustered into 2 groups, one classical/exocrine-like, and the other squamous-like; and (6) SRC carcinoma-derived organoids can be successfully generated, and their cultures preserve the histologic and molecular features of parental SRC carcinoma. Although pancreatic SRC carcinoma shares similarities with conventional PDAC regarding the most important genetic drivers, it also exhibits important differences. A personalized approach for patients with this tumor type should consider the clinical relevance of histologic determination of the SRC component and the presence of potentially actionable molecular targets.

Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour-stromal cell interactions. So far, the pre-clinical studies have suggested that PDT can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. However, the complexity of this interplay, including the combined tumour promoting and suppressing effects, poses unknowns for the clinical application of photodynamic stromal depletion in PDAC.

This study aimed to investigate the effectiveness of tumor markers and contrast-enhanced computed tomography (CE-CT) in differentiating gastric hepatoid adenocarcinoma (GHA) from gastric adenocarcinoma (GA).

This retrospective study included 160 patients (44 with GHA vs. 116 with GA) who underwent preoperative CE-CT. Preoperative serum concentrations of tumor biomarkers and CT imaging features were analyzed, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), tumor location, growth pattern, size, enhancement pattern, cystic changes, and mass contrast enhancement. Multivariate logistic regression analyses were performed to evaluate useful tumor markers and CT imaging features for differentiating GHA from GA.

When compared to GA, GHA showed a higher serum AFP [13.27 ng/ml (5.2-340.1) vs. 2.7 ng/ml (2.2-3.98), P <0.001] and CEA levels [4.07 ng/ml (2.73-12.53) vs. 2.42 ng/ml (1.38-4.31), P <0.001]. CT imaging showed GHA with a higher frequency of tumor location in the gastric antrum (P <0.001). GHA had significantly lower attenuation values at the portal venous phase [PCA, (82.34 HU ± 8.46 vs. 91.02 HU ± 10.62, P <0.001)] and delayed phase [DCA, (72.89 HU ± 8.83 vs. 78.27 HU ± 9.51, P <0.001)] when compared with GA. Multivariate logistic regression analyses revealed that tumor location, PCA, and serum AFP level were independent predictors of differentiation between GHA and GA. The combination of these three predictors performed well in discriminating GHA from GA, with an AUC of 0.903, a sensitivity of 86.36%, and a specificity of 81.90%.

Integrated evaluation of tumor markers and CT features, including tumor location, PCA, and serum AFP, allowed for more accurate differentiation of GHA from GA.

A new biliary duct (BD) stricture raises questions about the presence of malignancy, especially with a history of metastatic pancreatic cancer. A few cases of colloid carcinoma (CC) of the pancreas have been published, but none have described recurrence in the biliary tract. We report a case of intrahepatic biliary CC that recurred after two years after the last dose of immunotherapy for pancreatic CC. In addition to a unique biliary cancer case presentation, this case raises awareness of the best strategy for cancer surveillance.

The detection of incidental pancreatic cystic lesions has increased over time. It is crucial to separate benign from potentially malignant or malignant lesions to guide management and reduce morbidity and mortality. The key imaging features used to fully characterize cystic lesions are optimally assessed by contrast-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography, with pancreas protocol computed tomography offering a complementary role. While some imaging features have high specificity for a particular diagnosis, overlapping imaging features between diagnoses may require further investigation with follow-up diagnostic imaging or tissue sampling.

Primary pancreatic signet ring cell carcinoma (PPSRCC) is a rare and aggressive tumor with poor prognosis. Here, we report a case of PPSRCC treated with curative surgery. A 49-year-old man presented with right mid-abdominal pain. Imaging tests showed a 3.6 cm tumor extending around the head of the pancreas, the second portion of the duodenum, and the retroperitoneum. Involvement of the right proximal ureter resulted in moderate right hydronephrosis. A subsequent tumor biopsy revealed suspected pancreatic adenocarcinoma. No apparent lymph node or remote metastases were observed. The tumor was considered resectable, and radical pancreaticoduodenectomy was planned. Pancreaticoduodenectomy, right nephroureterectomy, and right hemicolectomy were conducted to resect the tumor en bloc. Final pathology revealed a poorly differentiated ductal adenocarcinoma of the pancreas with signet ring cells infiltrating the right ureter and transverse mesocolon (pT3N0M0, stage IIA, according to UICC for International Cancer Control TNM classification). The postoperative course was uneventful, and oral fluoropyrimidine (S-1) was administered as adjuvant chemotherapy for 1 year. At the 16-month follow-up, the patient was alive without any evidence of recurrence. Pancreaticoduodenectomy with right hemicolectomy and right nephroureterectomy was performed for curative resection of PPSRCC infiltrating the transverse mesocolon and right ureter.

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, currently has a dismal five-year survival rate of approximately 10% due to late diagnosis and a lack of efficient treatment options such as surgery. Furthermore, the majority of PDAC patients have surgically unresectable cancer, meaning cancer cells have either reached the surrounding blood vessels or metastasized to other organs distant from the pancreas area, resulting in low survival rates as compared to other types of cancers. In contrast, the five-year survival rate of surgically resectable PDAC patients is currently 44%. The late diagnosis of PDAC is a result of little or no symptoms in its early stage of development and a lack of specific biomarkers that may be utilized in routine examinations in the clinic. Although healthcare professionals understand the importance of early detection of PDAC, the research on the subject has lagged and no significant changes in the death toll of PDAC patients has been observed. This review is focused on understanding potential biomarkers that may increase the early diagnosis of PDAC patients at its surgically resectable stage. Here, we summarize the currently available biomarkers used in the clinic as well as those being developed with the hope of providing insight into the future of liquid biomarkers to be used in routine examinations for the early diagnosis of PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas, accounting for more than 90% of all pancreatic malignancies. As a highly lethal malignancy, PDAC is the fourth leading cause of cancer-related deaths worldwide with a 5-year overall survival of less than 8%. The efficacy and outcome of PDAC treatment largely depend on the stage of disease at the time of diagnosis. Surgical resection followed by adjuvant chemotherapy remains the only possibly curative therapy, yet 80%-90% of PDAC patients present with nonresectable PDAC stages at the time of clinical presentation. Despite our advancing knowledge of PDAC, the prognosis remains strikingly poor, which is primarily due to the difficulty of diagnosing PDAC at the early stages. Recent advances in glycoproteomics and glycomics based on mass spectrometry have shown that aberrations in protein glycosylation plays a critical role in carcinogenesis, tumor progression, metastasis, chemoresistance, and immuno-response of PDAC and other types of cancers. A growing interest has thus been placed upon protein glycosylation as a potential early detection biomarker for PDAC. We herein take stock of the advancements in the early detection of PDAC that were carried out with mass spectrometry, with special focus on protein glycosylation.

The study aimed to investigate the effects of lipopolysaccharide (LPS) alone and in combination with calorie restriction (CR) on the pancreatic tissues in C57BL/6 mice modeled with pancreatic ductal adenocarcinoma (PDAC). Forty male C57BL/6 mice (10-13 weeks old) were divided into five groups; LPS, LPS + CR, PDAC, PDAC + LPS, and PDAC + LPS + CR. Nuclear factor kappa B (NF-κβ), interleukin-6 (IL-6), and c-Jun N-terminal kinases (JNK) mRNA expression levels were measured in pancreatic tissues. NF-κβ, IL-6, JNK, and proliferating cell nuclear antigen (PCNA) peptide levels were determined by immunohistochemistry. Oxidative stress markers and antioxidant enzyme activities were determined spectrophotometrically. TH1/TH2 cytokine measurements were determined by a flow cytometer. It was detected that the number of PCNA immune + cells in the PDAC + LPS + CR group was significantly lower than in the PDAC and PDAC + LPS groups (p < 0.01, p < 0.05 respectively). PDAC + LPS + CR group's plasma interferon-gamma (IFN-γ), IL-6, IL-2, tumor necrosis factor-alpha, IL-3, and IL-4 levels were found to be significantly lower than the PDAC group (p < 0.01, p < 0.001, p < 0.01, p < 0.05, p < 0.01, and p < 0.05 respectively). According to our findings, the combination of low-dose LPS and 40% CR was found to be more effective in PDAC model mice.

As a malignant tumor, pancreatic cancer has an extremely low overall 5-year survival rate. Pancreatic adenosquamous carcinoma (PASC), a rare pancreatic malignancy, owns clinical presentation similar to pancreatic ductal adenocarcinoma (PDAC), which is the most prevalent pancreatic cancer subtype. PASC is generally defined as a pancreatic tumor consisting mainly of adenocarcinoma tissue and squamous carcinoma tissue. Compared with PDAC, PASC has a higher metastatic potential and worse prognosis, and lacks of effective treatment options to date. However, the pathogenesis and treatment of PASC are not yet clear and are accompanied with difficulties.

The present paper systematically summarizes the possible pathogenesis, diagnosis methods, and further suggests potential new treatment directions through reviewing research results of PASC, including the clinical manifestations, pathological manifestation, the original hypothesis of squamous carcinoma and the potential regulatory mechanism. In short, the present paper provides a systematic review of the research progress and new ideas for the development mechanism and treatment of PASC.

To evaluate the diagnostic performance of radiomics model based on fully automatic segmentation of pancreatic tumors from non-enhanced magnetic resonance imaging (MRI) for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC).

In this retrospective study, patients with surgically resected histopathologically confirmed PASC and PDAC who underwent MRI scans between January 2011 and December 2020 were included in the study. Multivariable logistic regression analysis was conducted to develop a clinical and radiomics model based on non-enhanced T1-weighted and T2-weighted images. The model performances were determined based on their discrimination and clinical utility. Kaplan-Meier and log-rank tests were used for survival analysis.

A total of 510 consecutive patients including 387 patients (age: 61 ± 9 years; range: 28-86 years; 250 males) with PDAC and 123 patients (age: 62 ± 10 years; range: 36-84 years; 78 males) with PASC were included in the study. All patients were split into training (n=382) and validation (n=128) sets according to time. The radiomics model showed good discrimination in the validation (AUC, 0.87) set and outperformed the MRI model (validation set AUC, 0.80) and the ring-enhancement (validation set AUC, 0.74).

The radiomics model based on non-enhanced MRI outperformed the MRI model and ring-enhancement to differentiate PASC from PDAC; it can, thus, provide important information for decision-making towards precise management and treatment of PASC.

In pancreatic cancer treatment, tumor stage-dependent chemotherapies are used to prolong overall survival. By measuring DNA promoter hypermethylation in the plasma of patients with stage IV pancreatic cancer, it was recently shown that promoter DNA methylation of the tumor suppressor gene SFRP1 has a high value for predicting failure of drug treatment with gemcitabine. In this study, we therefore aimed to identify as precisely as possible the region in the SFRP1 promoter that is frequently hypermethylated in pancreatic cancer tissue. First, we used the TCGA data set to define CpG-rich regions flanking the SFRP1 transcription start site that were significantly more methylated in pancreatic cancer compared to normal pancreatic acinar tissue. A core CpG island was identified that exhibited abundant tumor DNA methylation and anti-correlation of SFRP1 mRNA expression. To validate our in silico results, we performed bisulfide conversion followed by DNA pyrosequencing of 28 matched formalin-fixed, paraffin-embedded (FFPE) pancreatic cancer cases and six pancreatic cancer cell lines. A defined block of seven CpG sites within the core CpG island was identified, which confirmed our in silico results by showing significantly higher SFRP1 methylation in pancreatic cancer specimens than in normal pancreatic tissue. By selecting this core CpG island, we were able to determine a median overall survival benefit for the low SFRP1 methylation group compared to the high SFRP1 methylation group (702 versus 517 days, p = 0.01) in the TCGA pancreatic cancer cohort. We propose a compact pyrosequencing assay that can be used in the future to further investigate the prognostic value of SFRP1 promoter hypermethylation in predicting pancreatic cancer chemoresistance. Therefore, instead of DNA analysis from blood (liquid biopsy), DNA easily extractable from cancer tissue blocks (FFPE material) could be used.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related deaths worldwide, accounting for 90% of primary pancreatic tumors with an average 5-year survival rate of less than 10%. PDAC exhibits aggressive biology, which, together with late detection, results in most PDAC patients presenting with unresectable, locally advanced, or metastatic disease. In-depth lipid profiling and screening of potential biomarkers currently appear to be a promising approach for early detection of PDAC or other cancers. Here, we isolated and characterized complex glycosphingolipids (GSL) from normal and tumor pancreatic tissues of patients with PDAC using a combination of TLC, chemical staining, carbohydrate-recognized ligand-binding assay, and LC/ESI-MS². The major neutral GSL identified were GSL with the terminal blood groups A, B, H, Le^a, Le^b, Le^x, Le^y, P1, and PX2 determinants together with globo- (Gb₃ and Gb₄) and neolacto-series GSL (nLc₄ and nLc₆). We also revealed that the neutral GSL profiles and their relative amounts differ between normal and tumor tissues. Additionally, the normal and tumor pancreatic tissues differ in type 1/2 core chains. Sulfatides and GM₃ gangliosides were the predominant acidic GSL along with the minor sialyl-nLc₄/nLc₆ and sialyl-Le^a/Le^x. The comprehensive analysis of GSL in human PDAC tissues extends the GSL coverage and provides an important platform for further studies of GSL alterations; therefore, it could contribute to the development of new biomarkers and therapeutic approaches.

The management of pancreatic ductal adenocarcinoma (PDAC) has evolved over the last two decades. Surgical resection remain the only potential cure for this cancer. Therefore, there is an emerging emphasis on neoadjuvant therapy to maximize the probability of resection, and identify failures early. The benefit of FOLFIRINOX in various clinical stages of PDAC have been practice changing. The addition of nab-paclitaxel to the traditional gemcitabine regimen added another option for treatment. In addition, immunotherapy and targeted therapies are applicable, based on molecular features and germline alterations; albeit, these are applicable to only a small minority of patients. In this review article, we discuss the key extant literature relevant to various stages of pancreatic cancer. We also summarize ongoing clinical trials which may guide future treatments.